Tumor-associated macrophages (TAMs) are M2-polarized macrophages that infiltrate the tumor microenvironment and promote tumorigenesis. However, the mechanisms by which TAMs modulate prostate cancer (PCa) growth are poorly understood. Here, we found that expression of Nephroblastoma Overexpressed (NOV/CCN3) is upregulated in PCa cells and correlated with M2 macrophage infiltration. RAW264.7 macrophage migration was induced by conditioned media (CM) from various PCa cells in proportion to the cellular level of CCN3 expression and was inhibited by an anti-CCN3 neutralizing antibody. CCN3 and PCaCM treatment skewed RAW264.7 cell differentiation from an M1 phenotype to an M2 phenotype. PCa-derived CCN3 induced focal adhesion kinase (FAK)/Akt/NF-κB signaling in RAW264.7 cells, which resulted in VEGF expression and subsequently increased tube formation in endothelial progenitor cells. Finally, PCa-secreted CCN3 stimulated RAW264.7 cells and promoted angiogenesis in the chick chorioallantoic membrane assay (CAM), and increased tumor growth and tumor-associated angiogenesis in a PCa xenograft mouse model. Our results indicate that PCa-secreted CCN3 can recruit macrophages and skew their differentiation to an M2 phenotype. In turn, CCN3-stimulated macrophages contribute to VEGF-dependent angiogenesis. This study reveals a novel mechanism by which TAMs enhance PCa angiogenesis and identifies a potential therapeutic target for PCa.

BackgroundThe traditional otorhinoendoscope is widely used in the diagnosis of a variety of ear and nose diseases, but only one doctor can use it at a time. It is also very difficult to share observations from one doctor with another doctor. With advances in electronic health technology, the extended potential application of smartphones to support medical practice or mobile health has grown steadily.ObjectiveThe first phase of the study discussed how smartphones may be used for otorhinoscopic imaging and image management via an innovative adaptor. The second phase of the study was to evaluate the diagnostic capability of the smartphone-based otorhinoendoscope, as compared to the traditional otorhinoendoscope, and its application in mobile health and teleotolaryngology.MethodsWe designed a unique adaptor to connect the otorhinoendoscope and smartphone in order to perform smartphone-based otorhinoendoscopy. The main aim was to transform the smartphone into an otorhinoendoscope. We devised a method that would allow us to use the smartphone’s camera to capture otorhinoscopic images. Using a freely available Web-based real-time communication application platform and the 3G (or WIFI) network, the smartphone-based otorhinoendoscope could synchronize the smartphone-based otorhinoscopic image with smartphones, tablet PCs, computer notebooks, or personal computers.ResultsWe investigated the feasibility of telemedicine using a smartphone, tablet PC, and computer notebook. Six types of clinical otorhinoscopic images were acquired via the smartphone-based otorhinoendoscope from six patients, which were examined in this study. Three teleconsultants (doctors A, B, and C) reviewed the six types of clinical otorhinoscopic images and made a telediagnosis. When compared to the face-to-face diagnosis, which was made in-person via a traditional otorhinoendoscope, the three teleconsultants obtained scores of a correct primary telediagnosis 83% (5/6), 100% (6/6), and 100% (6/6) of the time, respectively. When the clinical data were provided, the three teleconsultants obtained a correct secondary telediagnosis score of 100% (6/6), 100% (6/6), and 100% (6/6) of the time, respectively.ConclusionsThe use of previously available technologies in the absence of any additional expensive devices could significantly increase the quality of diagnostics while lowering extraneous costs. Furthermore, this could also increase the connectivity between most isolated family doctors and remote referral centers.

PurposeTo characterize the impact of comorbidity on survival outcomes for patients with nasopharyngeal carcinoma (NPC) post radiotherapy (RT).MethodsA total of 4095 patients with NPC treated by RT or RT plus chemotherapy (CT) in the period from 2007 to 2011 were included through Taiwan’s National Health Insurance Research Database. Information on comorbidity present prior to the NPC diagnosis was obtained and adapted to the Charlson Comorbidity Index (CCI), Age-Adjusted Charlson Comorbidity Index (ACCI) and a revised head and neck comorbidity index (HN-CCI). The prevalence of comorbidity and the influence on survival were calculated and analyzed.ResultsMost of the patients (75%) were male (age 51±13 years) and 2470 of them (60%) had at least one comorbid condition. The most common comorbid condition was diabetes mellitus. According to these three different comorbidity index (CCI, ACCI and HN-CCI), higher scores were associated with worse overall survival (P< 0.001). The Receiver Operating Characteristic (ROC) curve was used to assess the discriminating ability of CCI, AACI and HN-CCI scores and it demonstrated the predictive ability for mortality with the ACCI (0.693, 95% CI 0.670–0.715) was superior to that of the CCI (0.619, 95% CI 0.593–0.644) and HN-CCI (0.545, 95%CI 0.519–0.570).ConclusionComorbidities greatly influenced the clinical presentations, therapeutic interventions, and outcomes of patients with NPC post RT. Higher comorbidity index scores accurately was associated with worse survival. The ACCI seems to be a more appropriate prognostic indicator and should be considered in further clinical studies.

Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by poor prognosis and a low survival rate. VEGF-A is the most established angiogenic factor involved in the angiogenic-regulated tumor progression. WISP-1/CCN4 is an extracellular matrix-related protein that belongs to the Cyr61, CTGF, Nov (CCN) family and regulates many biological functions, such as angiogenesis. Previous studies indicated the role of WISP-1 in tumor progression. However, the angiogenic property of WISP-1 in the cancer microenvironment has never been discussed. Here, we provide novel insights regarding the role of WISP-1 in the angiogenesis through promoting VEGF-A expression. In this study, the correlation of WISP-1 and VEGF-A was confirmed by IHC staining of specimens from patients with OSCC. In vitro results indicated that WISP-1 induced VEGF-A expression via the integrin αvβ3/FAK/c-Src pathway, which transactivates the EGFR/ERK/HIF1-α signaling pathway in OSCC. This pathway in turn induces the recruitment of endothelial progenitor cells and triggers the neovascularization in the tumor microenvironment. Our in vivo data revealed that tumor-secreted WISP-1 promoted the angiogenesis through VRGF expression and increased angiogenesis-related tumor growth. Our study offers new information that highlights WISP-1 as a potential novel therapeutic target for OSCC.